New strategies to deliver anticancer drugs to brain tumors

Background: Malignant brain tumors are among the most challenging to treat and at present there are no uniformly successful treatment strategies. Standard treatment regimens consist of maximal surgical resection followed by radiotherapy and chemotherapy. The limited survival advantage attributed to chemotherapy is partially due to low CNS penetration of antineoplastic agents across the blood–brain barrier (BBB). Objective: The objective of this paper is to review recent approaches to delivering anticancer drugs into primary brain tumors. Methods: Both preclinical and clinical strategies to circumvent the BBB are considered that include chemical modification and colloidal carriers. Conclusion: Analysis of the available data indicates that new approaches may be useful for CNS delivery, yet an appreciation of pharmacokinetic issues and improved knowledge of tumor biology will be needed to affect significantly drug delivery to the target site.     

TAT介导的几种纳米药物载体的研究概况

TAT是一种应用最早且现今最为常用的细胞穿膜肽,已经成功与多种纳米载体如脂质体、胶束、纳米粒等连结形成可内化进入细胞内的载药体系。文章主要对TAT介导的几种纳米载药体系的穿透机制、体内外抗肿瘤活性及靶向病变部位能力等方面的研究进行综述,同时对微环境pH敏感的TAT靶向药物载体的研究进展作了简单介绍。     

Tumor delivery of macromolecular drugs based on the EPR effect

Enhanced permeability and retention (EPR) effect is the physiology-based principal mechanism of tumor accumulation of large molecules and small particles. This specific issue of Advanced Drug Delivery Reviews is summing up multiple data on the EPR effect-based drug design and clinical outcome. In this commentary, the role of the EPR effect in the intratumoral delivery of protein and peptide drugs, macromolecular drugs and drug-loaded long-circulating pharmaceutical nanocarriers is briefly discussed together with some additional opportunities for drug delivery arising from the initial EPR effect-mediated accumulation of drug-containing macromolecular systems in tumors.     

Nanocarriers

The use of nanoparticulate pharmaceutical carriers to enhance the in vivo efficiency of many drugs well established itself over the past decade both in pharmaceutical research and clinical setting. The current level of engineering pharmaceutical nanocarriers in some cases allows for drug delivery systems (DDS) to demonstrate a combination of some desired properties. However, looking into the future of the field of drug delivery, we have to think about the development of the next generation of pharmaceutical nanocarriers combining different properties and allowing for multiple functions.     

Development of nanoparticulate systems with action in breast and ovarian cancer: nanotheragnostics

Abstract

The use of nanoparticulate systems with action in breast and ovarian cancer has been highlighted in recent years as an alternative to increasing the therapeutic index of conventional anticancer drugs. Thus, nanoparticles have advantageous characteristics in the treatment of cancer. Several nanocarriers of drugs and nanoparticles are described in the literature. The pharmacokinetics of the drugs can be modified by the use of nanocarriers, which in turn facilitate the specific delivery of the drug to the tumour cell. Therefore, the present work is a review that examines some nanosystems with nanoparticles for action in the treatment of breast cancer and ovarian cancer.     

Role of CD44 in tumour progression and strategies for targeting

CD44 or hyaluronan receptor is a transmembrane receptor associated with aggressive tumour growth, proliferation, and metastasis. In normal physiology, this receptor has a crucial role in cell adhesion, inflammation, and repair processes. However, many tumour cells over-express this receptor and abuse it to become progressive and perpetual units. The article comments from common functioning of the CD44 receptor, to its diabolic multi-dimensional effects in promotion of malignant cells. It also illuminates the relations of CD44 endorsed processes with other biomolecular events in cancer progression. In an end, the review focuses comprehensively at ongoing researches to exploit the CD44 over-expression as a probable target in treatment, management, and diagnosis of malignancy.     

Gold-capped mesoporous silica nanoparticles as an excellent enzyme-responsive nanocarrier for controlled doxorubicin delivery

Abstract

Mesoporous silica nanoparticles (MSNs) have ideal characteristics as next generation of controlled drug delivery systems. In this study, a MSN-based nanocarrier was fabricated and gold nanoparticle (GNP)-biotin conjugates were successfully grafted onto the pore outlets of the prepared MSN. This bioconjugate served as a capping agent with a peptide-cleavable linker sensitive to matrix metalloproteinases (MMPs), which are overexpressed extracellular proteolytic enzymes in cancerous tissue. The prepared nanocarriers were fully characterised by scanning electron microscopy (SEM), transmission electron microscopy (TEM), nitrogen adsorption/desorption, Fourier transform infra-red spectroscopy (FTIR), dynamic light scattering (DLS) and thermo gravimetric analysis (TGA). In vitro release studies showed efficient capping of MSNs with gold gate and controlled release of Doxorubicin (DOX) in the presence of matrix metalloproteinase-2 (MMP-2) and acidic pH values. High DOX-loading capacity (21%) and encapsulation efficiency (95.5%) were achieved using fluorescence technique. DOX-loaded nanocarriers showed high cytocompatibility and could efficiently induce cell death and apoptosis in the MMP-2 overexpressed cell lines. Moreover, Haemolysis, platelet activation and inflammatory responses assessment approved excellent hemocompatibility and minimal side effects by encapsulation of DOX in MSNs carrier.     

Intranasal infusion of nanostructured lipid carriers (NLC) containing CNS acting drug and estimation in brain and blood

Abstract

The present study was aimed to evaluate the nanostrucured lipid carriers (NLC) containing duloxetine (DLX-NLC) for intranasal infusion through the nasal cavity of rat. The in vivo nasal infusion studies were performed using Wistar rats and the amount of DLX permeated and its amount in brain and blood was estimated. The effects on absorption rate and type of drug delivery systems (nanocarriers and drug solution) for nose to brain/blood permeation were assessed. DLX was found to be permeated from the nasal cavity into the body of rat and the permeated amount was found to be more in case of DLX-NLC. Approximately 2.5-times better permeation was exhibited by DLX-NLC than DLX-solution. Appreciable amount of DLX was estimated in blood and brain and the estimated amount was higher in case of DLX-NLC. Thus the administration of NLC containing DLX through intranasal route was found to be potential method for the delivery of DLX for the treatment of depression.     

Cleavable PEGylation: a strategy for overcoming the “PEG dilemma” in efficient drug delivery

To prolong the circulation time of drug, PEGylation has been widely used via the enhanced permeability and retention (EPR) effect, thereby providing new hope for better treatment. However, PEGylation also brings the "PEG dilemma", which is difficult for the cellular absorption of drugs and subsequent endosomal escape. As a result, the activity of drugs is inevitably lost after PEG modification. To achieve successful drug delivery for effective treatment, the crucial issue associated with the use of PEG-lipids, that is, “PEG dilemma” must be addressed. In this paper, we introduced the development and application of nanocarriers with cleavable PEGylation, and discussed various strategies for overcoming the PEG dilemma. Compared to the traditional ones, the vehicle systems with different environmental-sensitive PEG-lipids were discussed, which cleavage can be achieved in response to the intracellular as well as the tumor microenvironment. This smart cleavable PEGylation provides us an efficient strategy to overcome “PEG dilemma”, thereby may be a good candidate for the cancer treatment in future.     

Applications of graphene oxide in case of nanomedicines and nanocarriers for biomolecules: review study

In this Review article, recent progress in matter of graphene oxide (GO) synthesis and its functionalization via a vast range of materials, including small molecules, polymers, and biomolecules, were reported and systematically summarized in order to overcome the inherent drawbacks of GO nanocarriers and thereby make these nanocarriers suitable for delivering chemotherapeutic agents, genes, and short interfering RNAs. Briefly, this work describes current strategies for the large scale production of GO and modification of graphene-based nanocarriers surfaces through practical chemical approaches, improving their biocompatibility and declining their toxicity. It also describes the most relevant cases of study suitable to demonstrate the role of graphene and graphene derivatives (GD) as nanocarrier for anti-cancer drugs and genes (e.g. miRNAs). Moreover, the controlled release mechanisms within the cell compartments and blood pH for targeted therapeutics release in the acidic environment of tumor cells or in intracellular compartments are mentioned and explored.